Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

TLDR

Chronic wounds such as venous ulcers exhibit delayed healing and high morbidity, and although surgical debridement is routinely performed to stimulate healing, it is often repeated because no objective biological markers guide the extent of tissue removal. The study aims to develop bioassays and molecular markers that can guide surgical debridement by assessing the pathogenesis of wound tissue before and after debridement, ultimately enabling more accurate and efficacious removal of non‑impaired tissue. Researchers obtained biopsies from three patients at the nonhealing edge before debridement and from adjacent nonulcerated skin after debridement, then evaluated histology, fibroblast migration, and gene expression profiles. Biopsies from nonhealing edges displayed hyperproliferative epidermis, dermal fibrosis, increased procollagen synthesis, and impaired fibroblast migration, whereas adjacent nonulcerated biopsies showed normalized morphology and migration; both sites possessed distinct, reproducible gene expression signatures, demonstrating that chronic ulcers contain subpopulations of cells with differing healing capacities that can be identified by gene expression profiling.

Abstract

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients' wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious.